The first version of this story appeared in the middle Quanta Magazine.
For the RNA molecule, the world is a dangerous place. Unlike DNA, which can last for millions of years with its remarkably stable, double-stranded structure, RNA is not designed to last—even inside a synthetic cell. Unless protectively bound to a larger molecule, RNA can degrade in minutes or less. And without a cell? Forget about it. Harmful, ubiquitous RNA-destroying enzymes are produced by all forms of life as a defense against viruses that encode their genes in the RNA code.
There is one way that RNA can survive outside the cell unharmed: in a small protective bubble. For decades, researchers have observed cells releasing these vesicles from the cell membrane, called extracellular vesicles (EVs), filled with damaged RNA, proteins, and other molecules. But these bags were considered little more than garbage bags that remove the waste of broken cells from the cell during normal excretion.
Then, in the early 2000s, experiments led by Hadi Valadi, a molecular biologist at the University of Gothenburg, revealed that the RNA inside some EVs didn’t look like junk. The cocktail of RNA sequences was very different from that found inside the cell, and this arrangement was consistent and efficient. When Valadi’s team exposed human cells to EVs from mouse cells, they were shocked to see the human cells take the RNA messages and “read” them to make functional proteins that they otherwise wouldn’t be able to make.
Valadi concluded that cells were packaging RNA strands into vesicles to communicate with each other. “When I was outside and saw that it was raining,” he said, “I can tell you: When you go out, take an umbrella with you.” In a similar way, he suggested, a cell could warn its neighbors of exposure to harmful bacteria or chemicals before they themselves encounter danger.
Since then, a wealth of evidence has emerged in support of this theory, fueled by advances in sequencing technology that allow scientists to detect and isolate small segments of RNA. Since Valadi published his experiments, other researchers have observed EVs filled with complex RNA complexes. These RNA sequences can contain detailed information about the host cell and trigger specific effects on recipient cells. The findings have led some researchers to suggest that RNA may be a molecular lingua franca that transcends the usual taxonomic boundaries and therefore can include messages that remain comprehensible throughout the medicine of life.
In 2024, new research has revealed additional layers of this story, showing, for example, that together with bacteria and eukaryotic cells, archaea also exchange vesicle-bound RNA, confirming that this practice is universal in all three domains of life. Other studies have expanded our understanding of the molecular communication of the kingdom by showing that plants and infecting fungi can use packets of RNA that cause damage as a form of evolutionary information warfare: The enemy cell reads the RNA and creates proteins that damage itself. molecular machinery.
“I was amazed at what RNA could do,” said Amy Buck, an RNA biologist at the University of Edinburgh who was not involved in the new research. To him, understanding RNA as a means of communication “goes beyond appreciating the complexity and dynamic nature of RNA within the cell.” Transmitting information outside the cell may be one of its internal roles.
Time Sensitive Delivery
Biologist Susanne Erdmann studies bacterial diseases in the Haloferax volcaniia single-celled organism that thrives in incredibly salty environments like the Dead Sea or the Great Salt Lake. Single-celled viruses are known to exchange EVs widely, but H. volcanii not a bacterium—an archaean, a member of the third evolutionary branch of life, consisting of cells that are structured differently from bacteria or eukaryotes like us.
Because EVs have the same size and density as virus particles, Erdmann’s group studies at the Max Planck Institute for Marine Microbiology in Germany, “they always show up when you isolate and purify bacteria,” he said. Eventually, his group got curious and decided to take a peek at what was inside.